Mechanisms linking hypertriglyceridemia to acute pancreatitis

Hypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important etiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG-induced AP and the clinically observed effects of HTG on the outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG-induced AP or AP in the presence of HTG and determining possible treatments are needed

Clinical Outcomes and Predictors of Thirty-Day Readmissions of Hypertriglyceridemia-Induced Acute Pancreatitis

Background: Hypertriglyceridemia (HTG) is a well-established cause of acute pancreatitis often leading to significant morbidity, mortality, and healthcare burden. This study aimed to describe the rate, reasons, and predictors of HTG-induced acute pancreatitis (HTG-AP) in the USA. Methods: This retrospective study analyzed the Nationwide Readmissions Database (NRD) for 2018 to determine all adults (≥ 18 years) readmitted within 30 days of an index hospitalization of HTG-AP. Hospitalization characteristics and adverse outcomes for 30-day readmissions were highlighted and compared with index admissions of HTG-AP. Furthermore, independent predictors for 30-day readmissions of HTG-AP were also identified. P values ≤ 0.05 were considered statistically significant. Results: In 2018, the rate of 30-day readmission of HTG-AP was noted to be 13.5%. At the time of readmission, AP (45.2%) was identified as the most common principal diagnosis, followed by chronic pancreatitis (6.3%) and unspecified sepsis (4.8%). Compared to index admissions, 30-day readmissions of HTG-AP had a higher proportion of patients with Charlson Comorbidity Index (CCI) scores ≥ 3 (48.5% vs. 33.8%, P < 0.001). Furthermore, we noted higher rates of inpatient mortality (1.7% vs. 0.7%, odds ratio (OR): 2.55, 95% confidence interval (CI): 1.83 - 3.57, P < 0.001), mean length of stay (LOS) (5.6 vs. 4.1 days, OR: 1.5, 95% CI: 1.2 - 1.7, P < 0.001), and mean total healthcare charge (THC) ($56,799 vs.$36,078, OR: 18,702, 95% CI: 15,136 - 22,267, P < 0.001) for 30-day readmissions of HTG-AP compared to index admissions. Independent predictors for 30-day all-cause readmissions of HTG-AP included hypertension, protein energy malnutrition (PEM), CCI scores ≥ 3, chronic kidney disease and discharge against medical advice. Conclusions: AP was the principal diagnosis on presentation in only 45.2% patients for 30-day readmissions of HTG-AP. Compared to index admissions, 30-day readmissions of HTG-AP had a higher comorbidity burden, inpatient mortality, mean LOS and mean THC

Role of short interval FLIP panometry in predicting long-term outcomes after per-oral endoscopic myotomy.

BACKGROUND: The Eckardt score (ES) is used to assess symptom response to Per-Oral Endoscopic Myotomy (POEM), but reliable methods to assess physiologic success are needed. Functional lumen imaging probe (FLIP) panometry has a potential role in post-POEM follow-up to predict long-term outcomes. The aim of this study was to assess the correlation between clinical success and FLIP parameters following POEM to determine if short interval FLIP could predict long-term outcomes. METHODS: This was a prospective study of adult patients who underwent POEM with short interval follow-up FLIP between 11/2017 and 3/2020. Clinical success was defined as post-procedure ES ≤ 3. Physiologic success was based on an esophago-gastric junction distensibility index (EGJ-DI) &gt; 2.8&nbsp;mm2/mmHg on FLIP. RESULTS: 47 patients (55% female, mean age 55&nbsp;years) were included in the study. Clinical success after POEM was seen in 45 (96%) patients (mean ES 6.5 ± 2.2 pre and 0.83 ± 1.0 post-POEM, p &lt; 0.001). Physiologic success was noted in 43 (91.5%) patients (mean EGJ-DI 6.1&nbsp;mm2/mmHg ± 2.5). Among 4 patients not meeting criteria for physiologic success, EGJ-DI was 2.5-2.6. There was no correlation between post-POEM EGJ-DI and ES in the short term or long term. Significant reflux esophagitis was seen in 6 (12.8%) patients with no difference in mean EGJ-DI with vs without esophagitis (5.9 vs 6.1, p = 0.44). CONCLUSION: Post-POEM endoscopy with FLIP is useful to both assess EGJ physiology and to examine for reflux esophagitis. Short interval FLIP has limited utility to predict long-term patient outcomes or risk of acid reflux

The Status of surgery in the management of high-risk prostate cancer

Although the optimal treatment for patients with high-risk prostate cancer remains unclear, combined radiotherapy and androgen-deprivation therapy (ADT) has become the standard of care; however, more recently, this paradigm has been challenged. In contemporary surgical series, using a multimodal approach with primary radical prostatectomy and adjuvant radiotherapy, when appropriate, had comparable efficacy in patients with high-risk disease to radiotherapy in combination with ADT. Furthermore, perioperative and postoperative morbidity associated with radical prostatectomy seem to be similar in patients with low-risk, intermediate-risk, or high-risk prostate cancer. Importantly, downstaging and downgrading of a substantial proportion of tumours after surgery suggests that many patients might be overtreated using radiotherapy and ADT. Indeed, the potential benefits of surgery include the ability to obtain tissues that can provide accurate histopathological information and, therefore, guide further disease management, in addition to local control of disease, a potentially reduced risk of developing metastases, and avoidance of long-term ADT. Thus, patients with high-risk disease should be offered a choice of first-line treatments, including surgery. However, effective management of high-risk prostate cancer is likely to require a multimodal approach, including surgery, radiotherapy, and neoadjuvant and adjuvant ADT, although the optimal protocols remain to be determined.10 page(s

Newer concepts in neural anatomy and neurovascular preservation in robotic radical prostatectomy

With more than 60% of radical prostatectomies being performed robotically, robotic-assisted laparoscopic prostatectomy (RALP) has largely replaced the open and laparoscopic approaches and has become the standard of care surgical treatment option for localized prostate cancer in the United States. Accomplishing negative surgical margins while preserving functional outcomes of sexual function and continence play a significant role in determining the success of surgical intervention, particularly since the advent of nerve-sparing (NS) robotic prostatectomy. Recent evidence suggests that NS surgery improves continence in addition to sexual function. In this review, we describe the neuroanatomical concepts and recent developments in the NS technique of RALP with a view to improving the "trifecta" outcomes